scholarly journals Efficacy and safety of bortezomib maintenance in patients with newly diagnosed multiple myeloma: a meta-analysis

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Chun-yan Sun ◽  
Jun-ying Li ◽  
Zhang-bo Chu ◽  
Lu Zhang ◽  
Lei Chen ◽  
...  

Multiple myeloma (MM) is a B-cell neoplasm with a high incidence of relapse. Bortezomib has been extensively studied for the maintenance treatment of MM. Here, we carried out a meta-analysis to determine the efficacy and safety of maintenance therapy with bortezomib. We searched for clinical trials in PubMed (Medline), Embase (OVID), and the Cochrane Library. Two randomized controlled trials (RCTs) enrolling a total of 1338 patients were included. Bortezomib maintenance statistically significantly improved both progression-free survival (PFS) (hazard ratio (HR) 0.67, 95% confidence interval (CI) = 0.51 to 0.87, P=0.003) and overall survival (OS) (HR = 0.75 therapy, 95% CI = 0.63 to 0.89, P=0.001) more than did non-bortezomib maintenance therapy. Our analysis revealed higher incidence of neutropenia (risks ratios (RR) = 1.39; 95% CI = 1.08 to 1.79), peripheral neuropathy (PN) (RR = 2.23; 95% CI = 1.38 to 3.61, P=0.001), and cardiologic events (RR = 1.91; 95% CI = 1.12 to 3.28, P=0.02) in patients with bortezomib maintenance therapy. Our meta-analysis demonstrates OS and PFS benefits of bortezomib maintenance therapy in patients with newly diagnosed MM. However, the therapy is associated with increased risk of adverse events. Additionally, more RCTs are needed for better understanding and determination of optimal bortezomib maintenance therapy in MM.

2018 ◽  
Vol 2 (13) ◽  
pp. 1608-1615 ◽  
Author(s):  
Sundar Jagannath ◽  
Rafat Abonour ◽  
Brian G. M. Durie ◽  
Mohit Narang ◽  
Howard R. Terebelo ◽  
...  

Abstract Autologous stem cell transplantation (ASCT) followed by lenalidomide maintenance therapy is the standard of care for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Clinical trials show progression-free survival (PFS) benefits, with some studies (Cancer and Leukemia Group [CALGB] trial and meta-analysis) also showing overall survival (OS) benefits, but applicability to real-world clinical settings is unclear. Using data from Connect MM, the largest US-based observational registry of NDMM patients, we analyzed effects of maintenance therapy on long-term outcomes in 1450 treated patients enrolled from 2009 to 2011. Patients who received induction therapy and ASCT (n = 432) were analyzed from 100 days post-ASCT (data cut 7 January 2016): 267 received maintenance (80% lenalidomide-based [of whom 88% received lenalidomide monotherapy]); 165 did not. Lenalidomide maintenance improved median PFS and 3-year PFS rate vs no maintenance (50.3 vs 30.8 months [hazard ratio (HR), 0.62; 95% confidence interval (CI), 0.46-0.82; P < .001] and 56% vs 42%, respectively). Improvements in median OS and 3-year OS rate were associated with lenalidomide maintenance vs no maintenance (not reached in either group [HR, 0.54; 95% CI, 0.36-0.83; P = .005] and 85% vs 70%, respectively). Five hematologic serious adverse events were reported with lenalidomide maintenance (pancytopenia [n = 2], febrile neutropenia, anemia, and thrombocytopenia [n = 1 each]) and 1 with no maintenance (thrombocytopenia). Second primary malignancies occurred at rates of 1.38 and 2.19 events per patient-year in lenalidomide maintenance and no maintenance groups, respectively. Survival benefits associated with lenalidomide maintenance previously demonstrated in clinical trials were observed in this community-based Connect MM Registry.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3776-3776
Author(s):  
Eunice Lai ◽  
Yu Yang Soon ◽  
Ainsley Ryan Yan Bin Lee ◽  
Shi Yin Wong ◽  
Cinnie Yentia Soekojo ◽  
...  

Abstract Background Maintenance therapy is considered a standard of care in transplant eligible (TE) and non transplant eligible (NTE) patients with newly diagnosed multiple myeloma (NDMM). While immunomodulators (IMID) and proteasome inhibitors (PI) have been proposed as maintenance therapy options, there are no randomised trials (RCTs) directly comparing these agents in the maintenance setting. The IMID lenalidomide (Len) and the PI ixazomib (Ixa) have been compared against placebo as maintenance strategies in NDMM. We present a network meta-analysis (NMA) of RCTs comparing the efficacy and safety of Len and Ixa maintenance therapies in NDMM. Methods We searched various biomedical databases for eligible studies evaluating Len or Ixa against placebo/ observation as maintenance therapy in patients with NDMM from date of inception through November 2020. The primary outcome was progression-free survival (PFS). Secondary outcomes include overall survival (OS) and adverse events (AE). The Cochrane risk of bias tool version 2.0 was used to assess trial quality. A Bayesian NMA model was used to assess the relative effects of competing treatments on PFS and OS outcomes. Adverse events were assessed using the synthesis without meta-analysis (SWIM) approach due to variability in the toxicity scoring criteria. The GRADE approach was used to rate the certainty of the evidence. This study is registered with PROSPERO, CRD42021226157. Results We identified eight studies including 3229 transplant eligible (TE) and 1689 non transplant eligible (NTE) patients. All studies were judged to have low risk of bias. Len but not Ixa was associated with statistically significant improvement in PFS when compared to placebo in TE (Len: Hazard Ratio (HR) 0.46, 95% Credible Interval (CrI) 0.35-0.56, high certainty; Ixa: HR 0.72, 95% CrI 0.46-1.13, moderate certainty) and NTE (Len: HR 0.46, 95% CrI 0.29-0.75, high certainty; Ixa: HR 0.69, 95% CrI 0.43-1.18, moderate certainty). Bayesian modelling demonstrated a 97% and 93% probability that Len resulted in superior PFS compared to Ixa in TE and NTE patients respectively. Both Len and Ixa were not associated with statistically significant improvement in OS compared to placebo in TE and NTE patients. There was no significant effect modification on the effect of Len vs placebo and Ixa vs placebo by cytogenetics status, use of proteasome inhibitors for induction or duration of maintenance therapies for PFS and/or OS outcomes. Len were judged to have a higher incidence of second malignancies and grade 3 or 4 neutropenia than Ixa while Ixa was judged to have a higher incidence of thrombocytopenia than Len. Conclusions Maintenance therapy with Len may provide a larger PFS benefit than Ixa regardless of type of induction therapy and cytogenetic risk in patients with NDDM. The differing toxicity profile of these agents is also an important consideration for treatment decisions. RCTs directly comparing these maintenance strategies are warranted. Figure 1 Figure 1. Disclosures Ooi: Jansen: Honoraria; Teva Pharmaceuticals: Honoraria; GSK: Honoraria; Abbvie: Honoraria; Amgen: Honoraria. Chng: Sanofi: Honoraria; Abbvie: Honoraria; Takeda: Honoraria; Amgen: Honoraria; BMS/Celgene: Honoraria, Research Funding; Johnson and Johnson: Honoraria, Research Funding; Pfizer: Honoraria.


Author(s):  
Hongyan Cheng ◽  
Junjun Yang ◽  
Huixin Liu ◽  
Yang Xiang

Abstract Purpose To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics. Methods We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer. Results We identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29–0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67–1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events). Conclusions PARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3292-3292
Author(s):  
Muhammad Abu Zar ◽  
Ahmad Kamal ◽  
Ali Younas Khan ◽  
Saad Ullah Malik ◽  
Mustafa Nadeem Malik ◽  
...  

Abstract Introduction: Daratumumab is a human IgGκ monoclonal antibody targeting CD38 that has been approved for the treatment of multiple myeloma (MM). We performed a meta-analysis of trials with daratumumab to find its efficacy and safety. Materials and Methods: Extensive literature search of Medline, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov on 5/07/2018 identified a total of 1596 articles. Fourteen articles (n = 1439) met the inclusion criteria, eleven in the relapsed and refractory multiple myeloma (RRMM) and three in the newly diagnosed multiple myeloma (NDMM) group (Table 1). A meta-analysis was performed using STATA version 15 and inter study heterogeneity was calculated using I² statistic. Results: The overall response rate (ORR) was 69% (95% CI: 51-84%) and very good partial response or better (≥VGPR) was 40% (95% CI: 22-60%) in RRMM patients. In a subgroup analysis with three, two and single drug regimen, ORR was 85% (95% CI: 77-92%), 30% (95% CI: 21-40%) and 31% (95% CI: 24-39%) respectively in RRMM patients. The hazard ratio (HR) for progression free survival (PFS) with daratumumab based regimens was 0.35 (95% CI: 0.26-0.45) as compared to non-daratumumab based regimens in two randomized controlled trials (RCTs). The most effective regimen, in terms of PFS for RRMM patients with a median of a single previous line of therapy was daratumumab with lenalidomide with dexamethasone (24-months PFS rate: 68%) in the POLLUX trial (Dimopoulos et al., 2017). The ORR was 97% (95% CI: 92-100%) and ≥VGPR rate was 64% (95% CI: 44-83%) in NDMM patients (Figure 1). In the only available RCT for NDMM patients, the HR for PFS was 0.50 (95% CI: 0.38-0.65) (Mateos et al., 2017). Incidence of neutropenia was 30% (95% CI: 16-46%) and thrombocytopenia was 25% (95% CI: 15-37%). While the incidence of anemia was 17% (95% CI: 13-21%). Incidence of ≥ grade 3 non-hematologic treatment emergent adverse effects (TEAEs) were as follows: pneumonia (11.3-12%), hypertension (8-12%) and fatigue (4-12.5%). In daratumumab and non-daratumumab based regimens ≥ grade 3 infusions related reactions occurred in 5% of the patients. In the three RCTs, these hematologic (≥ grade 3) TEAEs were comparable as neutropenia occurred in 36.86% vs 29.57%, thrombocytopenia in 30% vs 29% and anemia in 16.67% vs 19% respectively. Patients on daratumumab based regimens who discontinued treatment due to TEAEs were 8.56% vs 9.93% on non-daratumumab based regimens in the three RCTs which shows that most of the treatment discontinuations was due to other drugs in the regimen. Conclusion: Our results suggest that daratumumab containing regimen is more effective than non-daratumumab based regimens for RRMM and NDMM patients. Three drug daratumumab based regimens are more effective when compared to two drug or daratumumab monotherapy regimens. The safety profile of daratumumab is favorable, which makes it an extremely useful drug. Despite limited data in NDMM patients, daratumumab based regimens appear to be highly effective. Further prospective randomized trials are needed to compare various daratumumab based regimens. Disclosures No relevant conflicts of interest to declare.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Ya-Wu Zhang ◽  
Feng-Xian Wei ◽  
Xue-Ping Qi ◽  
Zhao Liu ◽  
Xiao-Dong Xu ◽  
...  

Objectives.To evaluate the efficacy and safety of endoscopic intralesional triamcinolone injection (ITI) for benign esophageal strictures combined with endoscopic dilation (ED).Methods.Online databases including MEDLINE, EMBASE, the Cochrane Library, and Web of Science were comprehensively searched for prospective randomized control trials (RCTs) between 1966 and March 2018. A meta-analysis was conducted according to the methods recommended by the Cochrane Collaboration.Results.Six RCTs consisting of 176 patients were selected. Meta-analysis results showed that additional ITI had a significant advantage in terms of stricture rate and required ED sessions. Surgery-related and non-surgery-related strictures showed similar results. Additional ITI was not associated with significantly increased risk of complications.Conclusions. Our meta-analysis showed that additional ITI therapy was supposed to be effective and safe for benign esophageal strictures as it reduced the stricture rate and required ED sessions. However, more RCTs are necessary to support these findings.


2020 ◽  
Vol 26 (44) ◽  
pp. 5739-5745
Author(s):  
Jieqiong Guan ◽  
Wenjing Song ◽  
Pan He ◽  
Siyu Fan ◽  
Hong Zhi ◽  
...  

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.


2021 ◽  
pp. 174749302110042
Author(s):  
Grace Mary Turner ◽  
Christel McMullan ◽  
Olalekan Lee Aiyegbusi ◽  
Danai Bem ◽  
Tom Marshall ◽  
...  

Aims To investigate the association between TBI and stroke risk. Summary of review We undertook a systematic review of MEDLINE, EMBASE, CINAHL, and The Cochrane Library from inception to 4th December 2020. We used random-effects meta-analysis to pool hazard ratios (HR) for studies which reported stroke risk post-TBI compared to controls. Searches identified 10,501 records; 58 full texts were assessed for eligibility and 18 met the inclusion criteria. The review included a large sample size of 2,606,379 participants from four countries. Six studies included a non-TBI control group, all found TBI patients had significantly increased risk of stroke compared to controls (pooled HR 1.86; 95% CI 1.46-2.37). Findings suggest stroke risk may be highest in the first four months post-TBI, but remains significant up to five years post-TBI. TBI appears to be associated with increased stroke risk regardless of severity or subtype of TBI. There was some evidence to suggest an association between reduced stroke risk post-TBI and Vitamin K antagonists and statins, but increased stroke risk with certain classes of antidepressants. Conclusion TBI is an independent risk factor for stroke, regardless of TBI severity or type. Post-TBI review and management of risk factors for stroke may be warranted.


2017 ◽  
Vol 45 (3) ◽  
pp. 924-932 ◽  
Author(s):  
Zeqing Bao ◽  
Chengmao Zhou ◽  
Xianxue Wang ◽  
Yu Zhu

Objective To evaluate the efficacy and safety of spinal anaesthesia using dexmedetomidine for caesarean section. Methods PubMed, The Cochrane Library, and CNKI were searched for relevant literature. Results The incidence of nausea and vomiting in the dexmedetomidine group was significantly lower than that in the control group (OR = 0.21, 95% CI: 0.12–0.35, P < 0.00001). No difference was found in the incidence of pruritus between the two groups (OR = 1.21, 95% CI: 0.36–4.09, P = 0.76).The dexmedetomidine group had a higher incidence of bradycardia than did the control group (OR = 2.20, 95% CI: 1.02–4.77, P = 0.05). The incidence of shivering in the dexmedetomidine group was significantly lower than that in the control group (OR = 0.20, 95% CI: 0.13–0.32, P < 0.00001). The incidence of hypotension was not different between the two groups (OR = 0.88, 95% CI: 0.49–1.56, P = 0.65). Conclusion Dexmedetomidine can decrease the incidence of nausea, vomiting, bradycardia, and shivering with spinal anaesthesia during caesarean section.


2021 ◽  
Vol 49 (8) ◽  
pp. 030006052110381
Author(s):  
Yin Wang ◽  
Yanqing Li ◽  
Ye Chai

Objective To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). Methods A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab. Results A total of seven RCTs were included ( n = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group. Conclusion The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 423
Author(s):  
Fausto Petrelli ◽  
Antonio Ghidini ◽  
Michele Ghidini ◽  
Roberta Bukovec ◽  
Francesca Trevisan ◽  
...  

Background: The modern concept of oligometastatic (OM) state has been initially developed to describe patients with a low burden of disease and with a potential for cure with local ablative treatments. We systematically assessed the risk of death and relapse of oligometastatic (OM) cancers compared to cancers with more diffuse metastatic spread, through a meta-analysis of published data.  Methods: PubMed, the Cochrane Library, and EMBASE were searched for studies reporting prognosis of patients with OM solid tumors. Risk of death and relapse were extracted and pooled to provide an adjusted hazard ratio with a 95% confidence interval (HR 95%CI).  The primary outcome of the study refers to overall mortality in OM vs. polymetastatic (PM) patients.  Results. Mortality and relapse associated with OM state in patients with cancer were evaluated among 104,234 participants (n=173 studies). Progression-free survival was better in patients with OM disease (hazard ratio [HR] = 0.62, 95% CI 0.57–0.68; P <.001; n=69 studies). Also, OM cancers were associated with a better overall survival (OS) (HR = 0.65, 95% CI 0.62-0.68; P<.01; n=161 studies). In colorectal (CRC), breast, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) the reduction in the risk of death for OM patients were 35, 38, 30 and 42%, respectively. Biliary tract and cervical cancer do not significantly better in OM stage likely for paucity of data. Conclusions. Patients with OM cancers have a significantly better prognosis than those with more widespread stage IV tumors. In OM cancer patients a personalized approach should be pursued.


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